
<ArticleTitle><prot>OX40</prot> stimulation by <prot>gp34</prot>/<prot>OX40 ligand</prot> enhances productive human immunodeficiency virus type 1 infection.</ArticleTitle>
<AbstractText><prot>OX40</prot> is a member of the tumor necrosis factor (TNF) receptor superfamily and known to be an important costimulatory molecule expressed on activated T cells. To investigate the role of costimulation of <prot>OX40</prot> in human immunodeficiency virus type 1 (HIV-1) infection by its natural ligand, <prot>gp34</prot>, the <prot>OX40</prot>-transfected ACH-2 cell line, ACH-2/<prot>OX40</prot>, chronically infected with HIV-1, was cocultured with paraformaldehyde (PFA)-fixed <prot>gp34</prot>-transfected mouse cell line, SV-T2/<prot>gp34</prot>. The results showed that HIV-1 production was strongly induced. This was followed by apparent apoptosis, and both processes were specifically inhibited by the <prot>gp34</prot>-specific neutralizing monoclonal antibody <prot>5A8</prot>. Endogenous <prot>TNF alpha</prot> (<prot>TNF-alpha</prot>) and <prot>TNF-beta</prot> production were not involved in the enhanced HIV-1 production. Furthermore, enhanced HIV-1 transcription in <prot>gp34</prot>-stimulated ACH-2/<prot>OX40</prot> cells was dependent on the kappa B site of the HIV-1 long terminal repeat, and the <prot>OX40</prot>-<prot>gp34</prot> interaction activated <prot>NF-kappa B</prot> consisting of <prot>p50</prot> and <prot>p65</prot> subunits. When primary activated <prot>CD4</prot>(+) T cells acutely infected with HIV-1(NL4-3) (<prot>CXCR4</prot>-using T-cell-line-tropic) were cocultured with PFA-fixed <prot>gp34</prot>(+) human T-cell leukemia virus type 1-bearing MT-2 cells or SV-T2/<prot>gp34</prot> cells, HIV-1 production was also markedly enhanced. The enhancement was again significantly inhibited by <prot>5A8</prot>. The present study first shows that <prot>OX40</prot>-<prot>gp34</prot> interaction stimulates HIV-1 expression and suggests that <prot>OX40</prot> triggering by <prot>gp34</prot> may play an important role in enhancing HIV-1 production in both acutely and latently infected <prot>CD4</prot>(+) T cells in vivo.</AbstractText>
